Nowadays the ageing problem is no longer limited to biological and medical aspects and begins to reach the level of the universal economic problem. In developed countries elderly people are already quantitatively prevail over youth, and the next 25 years the proportion of elderly people in the world will increase by 80% and the proportion of working-age population will decrease accordingly. (Dominguez L. J. Ageing, lifestyle modifications, and cardiovascular disease in developing countries. //J. Nutr. Health Aging, 2006, 10, 2, 143-9). It is obvious that such demographic changes will affect all spheres of life. Mankind will face an acute shortage of resources needed to address the ageing population problems and development issues in general, and therefore the problem of decelerating the human ageing and preventing the development of senile diseases is becoming increasingly important.
Ageing is a comprehensive and complex process accompanied by dysfunctions in the functioning of critical systems of regulation at the level of the whole organism, at the cellular and molecular levels. Such changes can be observed in various systems of the organism, such as the nervous system (decrease in brain mass, the size and density of neurons, the fall of the bioelectric activity of nerve cells, changes in behavior and learning ability, lipofuscin deposition), the digestive system (e.g., reduction of secretory activity of the digestive organs), the secretory system (reduction of basic renal function), the cardiovascular system (reduction of contractile capacity of the myocardium, increase in systolic blood pressure, slowing of heart rhythmic activity). Also, visual acuity and accommodative power of the eye are reduced, degenerative changes in the retina and cornea are accelerated. There are a slowdown and decrease in protein biosynthesis, increased fat content in various tissues and blood, change in lipid fractions ratio, increase in the frequency of lower tolerance towards carbohydrates and insulin supply to the organism. Degenerative processes in the skeleton (osteoporosis) are accelerated.
It is generally accepted that the slow poisoning of the organism by toxic oxygen species (ROS) plays a key role in the processes of ageing (V. P. Skulachev (2003) Aging and the programmed death phenomena. In: Topics in Current Genetics, Vol. 3 (T. Nystrom and H. D. Osiewacz, Eds.) Model systems in ageing. Springer-Verlag Berlin Heidelberg, pp. 191-238; V. P. Skulachev (2005) Aging as an atavistic program that we can attempt to cancel. Herald of the Russian Academy of Sciences (in Russian) 75, 831-843). High levels of antioxidants (such as vitamins A and E) in the organism are known to be characteristic of long-livers (Mecocci et al. Plasma antioxidants and longevity: a study on healthy centenarians //Free Radical Biology and Medicine, 2000, 28, 8, 1243-48); on the contrary, genetically determined dysfunctions in the antioxidant systems of the organism lead to accelerated ageing and reduction of the average life expectancy (Liu, J. & Mori A. Age-associated changes in superoxide dismutase activity, thiobarbituric acid reactivity and reduced glutathione level in the brain and liver in senescence accelerated mice (SAM): A comparison with ddY mice. //Mech. Aging Dev., 1993, 71, 23-30). Attempts to fight against senile diseases, and, ultimately, postpone ageing and death of the organism have been made repeatedly. The approaches used so far to strengthen the antioxidant protection have a positive effect mainly on various ageing-associated diseases, however both average life expectancy and maximum life span usually does not increase (Holloszy J. O. Longevity of exercising male rats: effect of an antioxidant supplemented diet. //Mechanisms of Ageing and Development, 1998, 100, 211-219; Orr, W. C. et al. Effects of overexpression of copper-zinc and manganese superoxide dismutases, catalase, and thioredoxin reductase genes on longevity in Drosophila melanogaster. //J Biol Chem., 200, 3 278 (29), 26418-26422). The data on antioxidant-induced extension of life span in the organisms with pathologically accelerated ageing, relative to normal members of their species, are the exception. For example, antioxidants can increase the average life expectancy of mice in a state of permanent oxidative stress due to dysfunctions in the ATM gene (Reliene R. & Schiestl R. Antioxidants Suppress Lymphoma and Increase Longevity in Atm-Deficient Mice //The Journal of Nutrition, 2007, 37, 229S-232S). According to the theory implying that ageing is part of the program(s) of the individual organism's development, low efficiency of the antioxidants used so far can be accounted for by organism's intention to fulfill the ageing program encoded in its genome despite our attempts to stop it. Indeed, the introduction of large doses of vitamin E appeared to induce the cytochrome P450 enzyme in liver microsomes which removes the excess antioxidant (Y. A. Sidorova, A. Y. Grishanova, V. V. Lyakhovich (2004). Transcriptional activation of cytochrome P450 1A1 with alpha-tocopherol. Bull Exp Biol Med., 138(3), 233-6.). Apart from the susceptibility to antioxidant-scavenging enzymes in the organism, traditional antioxidants have a disadvantage that they are uniformly distributed throughout the cell volume, rather than accumulate in the mitochondria responsible for generating the bulk of ROS in the organism.
Many known remedies increase the average life expectancy (ALE) of animals and humans. However the maximum life span (MLS) is not increased which implies that these remedies are aimed at correcting the pathological consequences of ageing, rather than the fundamental processes of ageing. Thus, mankind has almost exhausted the possibilities of extending the life span by traditional medicines, and in the first place there is a problem of developing means and methods of a radical impact on the ageing process. In this case, the term “the fight against ageing” implies decelerating, stopping or reversing the process of the entirety of the organism's dysfunctions causing the ageing, extending the life time, prevention or correction of dysfunctions that accompany the ageing process, in order to increase the length of productive life, and postpone these senile dysfunctions to a later date (or even cancel them).
The assumption of the possible effect of increasing life span and decelerating ageing induced by described compounds of structure (1) was also made in the patent application of the author of the given invention registered under the number RU 2005132217 dated Oct. 19, 2005. However, the experimental examples shown in the given patent application are only vaguely related to both the problem of extending the life time in general and specific senile diseases, and do not allow to state the usefulness of compounds of structure (1) in the fight against ageing as such.